Will the new malaria drug truly be able to eliminate drug-resistant parasites?

Mak Wen Yao , 26 Sep 2017

WHO stated that the burden of malaria was highest in sub-Saharan Africa.

Researchers from Tulane University School of Public Health and Tropical Medicine successfully developed a new drug to combat non-severe cases of malaria, according to results from an FDA-supervised clinical trial.

The molecule, AQ-13 was shown to be non-inferior to the standard treatment regimen of artemether with lumefantrine. This was a significant finding as experts have long warned about Plasmodium falciparum, the malaria-causing parasite’s developing resistance to conventional treatments.

The new drug molecule was tested in 66 Malian men diagnosed with non-complicated malaria, of which specifically, infections with Plasmodium falciparum. The study participants were randomised to receive either the standard treatment with artemether and lumefantrine, or to receive AQ-13, for three days.

The study drug was shown to eliminate the parasites responsible for the disease within a week, thus demonstrating a matching effectiveness to the standard malaria treatment.

An ancient scourge in the new millennium

Humankind has recorded malaria infections for millennia – from ancient Chinese medical writing to historical records of the Classical Greek civilisation. The centuries-old scourge has been widely referenced as the culprit behind population decline in city-states and rural areas alike.

World Health Organization (WHO) statistics indicated that, in 2015, almost half of the global population was at risk of malaria infection. Although the burden of disease was highest in sub-Saharan Africa, many regions in South-East Asia, Latin America and the Middle East were designated as “at risk” territories.

Malaria remains a public health concern in Malaysia, but the country is moving towards disease elimination through the implementation of the National Strategic Plan for Malaria Elimination. Development of parasite resistance towards standard treatment regimen remains a formidable challenge in the nation’s fight against the disease.

The scenario is consistent with the global picture, where the widespread resistance of P. falciparum towards chloroquine and sulfadoxine-pyrimethamine threatens to reverse any gains in the fight against malaria.

AQ-13 a stepping stone for other related compounds against drug-resistant parasites

Preclinical studies showed that AQ-13 was active against both chloroquine-resistant and chloroquine-susceptible P. falciparum, and demonstrated satisfactory safety in healthy human volunteers.

“The clinical trial results are extraordinarily encouraging. Compared to the current first-line recommendation for treatment of malaria, the new drug comes out very well,” explained Dr Donald Krogstad, senior author and professor of tropical medicine at Tulane University.

The success of the study also promoted the further understanding of modified 4-aminoquinolines (4-AQs) – such as the AQ-13 – where it could be a valuable tool in existing arsenal against drug-resistant parasites.

"The potential long-term implications are bigger than one drug," said Dr Krogstad.

Moving forward, the researchers hope to expand their trial of AQ-13 into other patient populations, including non-immune patients, women and children to safeguard patient's welfare before the introduction of the drug into the general population.

Too good to be true?

Critics such as Shanks and Möhrle, from Medicines for Malaria Venture, a not-for-profit organization, are sceptical over the success of AQ-13 in the phase-2 clinical trial. Primarily, the authors questioned the justification for the further development of the molecule.

Firstly, AQ-13 was only tested in male patients with uncomplicated malaria, therefore, there is the necessity to evaluate the compound in non-immune individuals (as a surrogate for infants) to provide an understanding of whether lower doses of AQ-13 can be used in combination with other treatment.

AQ-13 will also need to show superiority over other aminoquinolines as well. Again, the authors raised the concern that AQ-13 should not be used as a sole treatment currently – a potential partner compound must be sought.

Shanks and Möhrle also highlighted that global attention is shifting from malaria control to elimination. They urged for any new anti-malaria drug to fulfil the requirement of eliminating instead of controlling the parasite.

As the authors wrote, "when the mission is to eliminate the last parasite and not just treat the disease, one needs antimalarial drugs safe enough for mass administration to asymptomatic populations and drugs able to kill latent forms in the liver and sexual transmission stages to the mosquito." MIMS

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